On February 7th, 2017 I had a deep open muscle biopsy of the left vastus intermedius. Despite being cautioned by my neurologist that, “the chances of the biopsy showing anything are pretty low, if at all”, it did show something. I wrote an in-depth article regarding my biopsy and you can read it here.
For those that don’t want to read the parent article to this follow up, the biopsy showed cytochrome oxidase negative fibers which are indicative of mitochondrial dysfunction often seen in mutated or damaged mitochondria. They also found a few fibers with increased succinate dehydrogenase staining. This was all stated in the pathologist’s report.
The pathologist recommended that the muscle tissue get sent off to a university lab for more testing. My neurologist vacillated. He had admitted that they don’t see many mitochondrial cases (despite the fact that most neuromuscular diseases are mitochondrial in origin). He couldn’t decide where to send my tissue for further testing. Finally, after waiting for several weeks, he punted my case to a geneticist that primarily deals with children.
For me this referral ended up being providence. I knew this geneticist from 18 years prior when our wonderful daughter that was born with a rarer form of Down syndrome. At the time I didn’t even know there were several types of Down syndrome. Our “Maggie” was born with a Robertsonian translocation of the 21st chromosome. Her translocation was rare and only about 350 people or so in the U.S. have this form of Down syndrome with this particular translocation, but I digress.
I knew this geneticist to be busy but also open minded. I got an appointment with his assistant, a PhD genetic counselor, who recommended that my entire mitochondrial DNA (mtDNA) be sequenced. They would compare the muscle biopsy findings with the genetic results and attempt to correlate causal genes.
In August 2017 I had my entire mtDNA sequenced by a company called GeneDX. My geneticist works closely with this company for both testing a research. My Geneticist was also going to have mtDNA studied for mutations. The results of the testing showed some pathogenic genes that could be expressing now, however they did not completely correlate with the muscle biopsy results.
For those of you who are science geeks, the mtDNA analysis showed mutations involving some genes that processes lipids something similar to a medium-chain acyl-CoA dehydrogenase (MCAD) deficiency.
My geneticist suspected that there are problems in the nuclear DNA (nDNA) and suggested whole exome sequencing. To make the results more accurate he is also sequencing my brother (floxed) and my sister (not floxed). He will use their results to compare in light of the biopsy and my symptoms.
My siblings have submitted their samples and hopefully we will have some tangible results in 6 to 8 weeks. He is pretty sure they will find some culprits (he said “if it is occurring in genes that we know about, we will find out”).
I will post another update when I have received the results from the whole exome sequencing and sibling comparison. For me it represents the culmination of 10 years of personal research into my particular case. Stay tuned as I promise to keep you updated.